Long-acting injectable ART to advance health equity: a descriptive analysis of US clinic perspectives on barriers, needed support and programme goals for implementation from applications to the ALAI UP Project.

INTRODUCTION: Approval of the first long-acting injectable antiretroviral therapy (LAI ART) medication heralded a new era of HIV treatment. However, the years since approval have been marked by implementation challenges. The "Accelerating Implementation of Multilevel Strategies to Advance Long-Acting Injectable for Underserved Populations (ALAI UP Project)" aims to accelerate the systematic and equitable delivery of LAI ART. METHODS: We coded and analysed implementation barriers according to the Consolidated Framework for Implementation Research (CFIR) domains, desired resources and programme goals from questionnaire short-answer responses by clinics across the United States responding to ALAI UP's solicitation to participate in the project between November 2022 and January 2023. RESULTS: Thirty-eight clinics responded to ALAI UP's solicitation. The characteristics of LAI ART as an innovation (cost, complexity of procurement, dosing interval, limited eligibility) precipitated and interacted with barriers in other CFIR domains. Barriers included obtaining coverage for the cost of medication (27/38 clinics) (outer setting); need for new workflows and staffing (12/38) and/or systems to support injection scheduling/coordination (16/38), transportation and expanded clinic hours (13/38) (inner setting); and patient (10/38) and provider (7/38) education (individuals). To support implementation, applicants sought: technical assistance to develop protocols and workflows (18/38), specifically strategies to address payor challenges (8/38); additional staff for care coordination and benefits navigation (17/38); opportunities to share experiences with other implementing clinics (12/38); patient-facing materials to educate and increase demand (7/38); and support engaging communities (6/38). Clinics' LAI ART programme goals varied. Most prioritized delivering LAI ART to their most marginalized patients struggling to achieve viral suppression on oral therapy, despite awareness that current US Food and Drug Administration approval is only for virally suppressed patients. The goal for LAI ART reach after 1 year of implementation ranged from ≤10% of patients with HIV on LAI ART (17/38) to ≥50% of patients (2/38). CONCLUSIONS: Diverse clinic types are interested in offering LAI ART and most aspire to use LAI ART to support their most vulnerable patients sustain viral suppression. Dedicated resources centred on equity and relevant to context and population are needed to support implementation. Otherwise, the introduction of LAI ART risks exacerbating, not ameliorating, health disparities.

Sex differences in sociodemographic, clinical, and laboratory variables in childhood asthma: A birth cohort study.

BACKGROUND: There are marked sex differences in the prevalence and severity of asthma, both during childhood and adulthood. There is a relative lack of comprehensive studies exploring sex differences in pediatric asthma cohorts. OBJECTIVE: To identify the most relevant sex differences in sociodemographic, clinical, and laboratory variables in a well-characterized large pediatric asthma cohort. METHODS: We performed a cross-sectional analysis of the Mayo Clinic Olmsted County Birth Cohort. In the full birth cohort, we employed a natural language processing algorithm based on the Predetermined Asthma Criteria for asthma ascertainment. In a stratified random sample of 300 children, we obtained additional pulmonary function tests and laboratory data. We identified the significant sex differences among available sociodemographic, clinical, and laboratory variables. RESULTS: Boys were more commonly diagnosed with asthma than girls and were younger at the time of asthma diagnosis. There were no sex differences in relation to socioeconomic status. We identified a male predominance in the presence of a tympanostomy tube and a female predominance in the history of pneumonia. A higher percentage of boys had an FEV1/FVC ratio <0.85. Blood eosinophilia and atopic sensitization were also more common in boys. Finally, boys had higher levels of serum periostin than girls. CONCLUSION: This study describes significant sex differences in a large pediatric asthma cohort. Overall, boys had earlier and more severe asthma than girls. Differences in blood eosinophilia and serum periostin provide insights into possible mechanisms of the sex bias in childhood asthma.

Clinical and Functional Studies of MTOR Variants in Smith-Kingsmore Syndrome Reveal Deficits of Circadian Rhythm and Sleep-Wake Behavior.

Heterozygous de novo or inherited gain-of-function mutations in the MTOR gene cause Smith-Kingsmore syndrome (SKS). SKS is a rare autosomal dominant condition, and individuals with SKS display macrocephaly/megalencephaly, developmental delay, intellectual disability, and seizures. A few dozen individuals are reported in the literature. Here, we report a cohort of 28 individuals with SKS that represent 9 MTOR pathogenic variants. We conducted a detailed natural history study and found pathophysiological deficits among individuals with SKS, in addition to the common neurodevelopmental symptoms. These symptoms include sleep-wake disturbance, hyperphagia, and hyperactivity, indicative of homeostatic imbalance. To characterize these variants, we developed cell models and characterized their functional consequences. We showed that these SKS variants display a range of mTOR activities and respond to the mTOR inhibitor, rapamycin, differently. For example, the R1480_C1483del variant we identified here and the previously known C1483F are more active than wild-type controls and less responsive to rapamycin. Further, we showed that SKS mutations dampened circadian rhythms and low-dose rapamycin improved the rhythm amplitude, suggesting that optimal mTOR activity is required for normal circadian function. As SKS is caused by gain of function mutations in MTOR, rapamycin was used to treat several patients. While higher doses of rapamycin caused delayed sleep-wake phase disorder in a subset of patients, optimized lower doses improved sleep. Our study expands the clinical and molecular spectrum of SKS and support further studies for mechanism-guided treatment options to improve sleep-wake behavior and overall health.

Let-7 restrains an oncogenic epigenetic circuit in AT2 cells to prevent ectopic formation of fibrogenic transitional cell intermediates and pulmonary fibrosis.

Analysis of lung alveolar type 2 (AT2) progenitor stem cells has highlighted fundamental mechanisms that direct their differentiation into alveolar type 1 cells (AT1s) in lung repair and disease. However, microRNA (miRNA) mediated post-transcriptional mechanisms which govern this nexus remain understudied. We show here that the let-7 miRNA family serves a homeostatic role in governance of AT2 quiescence, specifically by preventing the uncontrolled accumulation of AT2 transitional cells and by promoting AT1 differentiation to safeguard the lung from spontaneous alveolar destruction and fibrosis. Using mice and organoid models with genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells, we demonstrate prevents AT1 differentiation and results in aberrant accumulation of AT2 transitional cells in progressive pulmonary fibrosis. Integration of enhanced AGO2 UV-crosslinking and immunoprecipitation sequencing (AGO2-eCLIP) with RNA-sequencing from AT2 cells uncovered the induction of direct targets of let-7 in an oncogene feed-forward regulatory network including BACH1/EZH2 which drives an aberrant fibrotic cascade. Additional analyses by CUT&RUN-sequencing revealed loss of let-7afd hampers AT1 differentiation by eliciting aberrant histone EZH2 methylation which prevents the exit of AT2 transitional cells into terminal AT1s. This study identifies let-7 as a key gatekeeper of post-transcriptional and epigenetic chromatin signals to prevent AT2-driven pulmonary fibrosis.

Antibiotic-associated neutropenia is marked by depletion of intestinal Lachnospiraceae in pediatric patients.

Hematologic side effects are associated with prolonged antibiotic exposure in up to 34% of patients. Neutropenia, reported in 10-15% of patients, increases the risk of sepsis and death. Murine studies have established a link between the intestinal microbiota and normal hematopoiesis. We sought to identify predisposing factors, presence of microbiota-derived metabolites, and changes in intestinal microbiota composition in otherwise healthy pediatric patients who developed neutropenia after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics and at the time of neutropenia. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and type of infection or type of antibiotic used; however intensive care unit admission and length of therapy were associated with neutropenia. Reduced intestinal microbiome richness and decreased abundance of Lachnospiraceae family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism and fatty acid metabolism that are known to be produced by Lachnospiraceae . Our study confirms a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis. As the microbiome is a key determinant of stem cell transplant and immunotherapy outcomes, these findings are likely to be of broad significance. Key Points: Neutropenia occurred in 17% of patients receiving prolonged antibiotic therapy.We found no association between neutropenia and type of infection or class of antibiotic used. Development of neutropenia after prolonged antibiotic treatment was associated with decreased prevalence of Lachnospiraceae and Lachnospiraceae metabolites such as citrulline.

Hemodynamic Comparison of the On-X and Top Hat Mechanical Aortic Valve Prostheses.

BACKGROUND: There are limited data comparing hemodynamic valve function in mechanical aortic valve prostheses. This study compared the hemodynamic function of 2 commonly used mechanical aortic valve (AV) prostheses, the On-X (Artivion) and Top Hat (CarboMedics Inc) valves. METHODS: This study was a retrospective analysis of 512 patients who underwent AV replacement with the On-X (n = 252; 49%) or Top Hat (n = 260; 51%) mechanical valves between 2011 and 2019. Patients were matched on the basis of selected variables. Echocardiographic data were collected preoperatively and postoperatively over a median follow-up of 1.39 years. RESULTS: A total of 320 patients were matched, 160 patients in each group. Despite being matched for left ventricular outflow tract diameter, patients in the Top Hat group received a greater prevalence of smaller tissue annulus diameter valves (≤21 mm) (83% vs 38%; P < .001). Patients in the On-X group had longer aortic cross-clamp times (78 minutes vs 64 minutes; P < .001) during isolated aortic valve replacement. Discharge echocardiography showed no difference in the AV area index between both groups (1.00 cm2/m2 vs 1.02 cm2/m2; P = .377). During longer-term echocardiographic follow-up, the AV area index remained stable for both valves within their respective tissue annulus diameter groups (P = .060). CONCLUSIONS: There was no difference between the 2 valves with respect to the AV area index at discharge, and hemodynamic function was stable during longer-term follow-up. The longer aortic cross-clamp time observed in the On-X group may indicate increased complexity of implantation compared with the Top Hat group.

Forged in the fire: Lasting impacts of inflammation on hematopoietic progenitors.

Quiescence and differentiation of hematopoietic stem and progenitor cells (HSPC) can be modified by systemic inflammatory cues. Such cues can not only yield short-term changes in HSPCs such as in supporting emergency granulopoiesis but can also promote lasting influences on the HSPC compartment. First, inflammation can be a driver for clonal expansion, promoting clonal hematopoiesis for certain mutant clones, reducing overall clonal diversity, and reshaping the composition of the HSPC pool with significant health consequences. Second, inflammation can generate lasting cell-autonomous changes in HSPCs themselves, leading to changes in the epigenetic state, metabolism, and function of downstream innate immune cells. This concept, termed "trained immunity," suggests that inflammatory stimuli can alter subsequent immune responses leading to improved innate immunity or, conversely, autoimmunity. Both of these concepts have major implications in human health. Here we reviewed current literature about the lasting effects of inflammation on the HSPC compartment and opportunities for future advancement in this fast-developing field.

Glucocorticoid response to naturalistic interactions between children and dogs.

Although research has shown that pets appear to provide certain types of social support to children, little is known about the physiological bases of these effects, especially in naturalistic contexts. In this study, we investigated the effect of free-form interactions between children (ages 8-10 years) and dogs on salivary cortisol concentrations in both species. We further investigated the role of the child-dog relationship by comparing interactions with the child's pet dog to interactions with an unfamiliar dog or a nonsocial control condition, and modeled associations between survey measures of the human-animal bond and children's physiological responses. In both children and dogs, salivary cortisol decreased from pre- to post-interaction; the effect was strongest for children interacting with an unfamiliar dog (compared to their pet dog) and for the pet dogs (compared to the unfamiliar dog). We found minimal evidence for associations between cortisol output and behaviors coded from video, but children scoring higher on survey measures of the human-animal bond exhibited the greatest reductions in cortisol when interacting with dogs. Self-reported loneliness was not related to cortisol or the human-animal bond, but measures of both loneliness and the human-animal bond were higher among children who participated after the onset of the COVID-19 pandemic, relative to those who participated before the pandemic. This study builds on previous work that investigated potential stress-buffering effects of human-animal interaction during explicit stressors and demonstrates important physiological correlates of naturalistic interactions between children and dogs, similar to those that occur in daily life.

Primary care professionals' perspectives on tailoring buprenorphine training for rural practice.

PURPOSE: Buprenorphine is a highly effective medication for opioid use disorder (OUD) that remains substantially underutilized by primary care professionals (PCPs). This is particularly true in rural communities, which have fewer prescribers and significant access disparities. The Drug Enforcement Administration removed the X-waiver requirement in December 2022, yet many rural clinicians still report barriers to prescribing buprenorphine. In this study, we examined rural PCPs' experiences with buprenorphine to identify tailored training strategies for rural practice. METHODS: Physicians, nurse practitioners, and physician associates practicing in rural Ohio counties were recruited through contacts at statewide health associations and health professions training programs. Twenty-three PCPs were interviewed about their perspectives on prescribing buprenorphine, including their training history. FINDINGS: PCPs self-reported being motivated to respond to OUD. However, they also reported that current training efforts failed to equip them with the knowledge and resources needed to prescribe effectively, and that urban-focused training often alienated rural clinicians. Participants suggested tailoring training content to rural settings, using rural trainers, and bolstering confidence in navigating rural-specific barriers, such as resource deficits and acute opioid fatigue. CONCLUSION: Our study found that current training on buprenorphine prescribing is inadequate for meeting the needs of rural PCPs. Tailored buprenorphine training is needed to improve accessibility and acceptability, and to better support the clinical workforce in communities disproportionately impacted by the opioid epidemic.

Blood and guts: how the intestinal microbiome shapes hematopoiesis and treatment of hematologic disease.

ABSTRACT: Over the past 10 years, there has been a marked increase in recognition of the interplay between the intestinal microbiome and the hematopoietic system. Despite their apparent distance in the body, a large literature now supports the relevance of the normal intestinal microbiota to steady-state blood production, affecting both hematopoietic stem and progenitor cells as well as differentiated immune cells. Microbial metabolites enter the circulation where they can trigger cytokine signaling that influences hematopoiesis. Furthermore, the state of the microbiome is now recognized to affect outcomes from hematopoietic stem cell transplant, immunotherapy, and cellular therapies for hematologic malignancies. Here we review the mechanisms by which microbiotas influence hematopoiesis in development and adulthood as well as the avenues by which microbiotas are thought to impact stem cell transplant engraftment, graft-versus-host disease, and efficacy of cell and immunotherapies. We highlight areas of future research that may lead to reduced adverse effects of antibiotic use and improved outcomes for patients with hematologic conditions.

Neurophysin I is an analytically robust surrogate biomarker for oxytocin.

Oxytocin is a pleiotropic neuropeptide that plays roles in biological processes ranging from birth, lactation, and social bonding to immune function, cardiovascular repair, and regulation of appetite. Although measurements of endogenous oxytocin concentrations have been performed for more than 50 years, the ability to measure oxytocin accurately poses notable challenges. One potential solution for overcoming these challenges involves measurement of oxytocin's carrier molecule - neurophysin I (NP-1) - as a surrogate biomarker. NP-1 is secreted in equimolar concentrations with oxytocin but has a longer half-life, circulates in higher concentrations, and can be measured using a sandwich immunoassay. We report experiments that 1) analytically validate a commercially available NP-1 sandwich immunoassay for use with human plasma and urine samples, 2) confirm the specificity of this assay, based on detection of NP-1 in plasma from wild-type but not oxytocin knockout mice, 3) demonstrate that NP-1 concentrations are markedly elevated in late pregnancy, consistent with studies showing substantial increases in plasma oxytocin throughout gestation, and 4) establish strong correlation between NP-1 and plasma oxytocin concentrations when oxytocin is measured in extracted (but not non-extracted) plasma. The NP-1 assay used in this study has strong analytical properties, does not require time-intensive extraction protocols, and the assay itself can be completed in < 2 h (compared to 16-24 h for a competitive oxytocin immunoassay). Our findings suggest that much like copeptin has become a useful surrogate biomarker in studies of vasopressin, measurements of NP-1 have similar potential to advance oxytocin research.

Over but not gone: lingering epigenetic effects of COVID-19.

'Long COVID' affects nearly one in five adults who have had coronavirus disease 2019 (COVID-19), yet the mechanisms underlying this disorder remain poorly understood. In a new study, Cheong et al. show that the epigenetic and transcriptional state of myeloid immune cells and their progenitors are durably altered in patients following severe COVID-19.

Hematopoietic stem and progenitor cells confer cross-protective trained immunity in mouse models.

Recent studies suggest that infection reprograms hematopoietic stem and progenitor cells (HSPCs) to enhance innate immune responses upon secondary infectious challenge, a process called "trained immunity." However, the specificity and cell types responsible for this response remain poorly defined. We established a model of trained immunity in mice in response to Mycobacterium avium infection. scRNA-seq analysis revealed that HSPCs activate interferon gamma-response genes heterogeneously upon primary challenge, while rare cell populations expand. Macrophages derived from trained HSPCs demonstrated enhanced bacterial killing and metabolism, and a single dose of recombinant interferon gamma exposure was sufficient to induce similar training. Mice transplanted with influenza-trained HSPCs displayed enhanced immunity against M. avium challenge and vice versa, demonstrating cross protection against antigenically distinct pathogens. Together, these results indicate that heterogeneous responses to infection by HSPCs can lead to long-term production of bone marrow derived macrophages with enhanced function and confer cross-protection against alternative pathogens.

Application of Innovative Subject Recruitment System for Batch Enrollment: A Pilot Study.

INTRODUCTION: Using a digital process that leverages electronic health records (EHRs) can ease many of the challenges presented by the traditional enrollment process for clinical trials. We tested if automated batch enrollment using a technology-enabled subject recruitment system (TESRS) enhances recruitment while preserving representation of research subjects for the study population in our study setting. METHODS: An ongoing community-based prospective adult cohort study was used to randomize 600 subjects who were eligible by age and residential address to TESRS (n = 300) and standard mailing method (n = 300), respectively, for 3 months. Then, TESRS was initiated and included automatic identification of patients' preference for being contacted (online patient portal vs postal mail) from EHRs and automatic sending out of invitation letters followed by completion of a short online survey for checking eligibility and the digital consent process if eligible. We compared (1) median time to consent from invitation sent out per subject and total subjects recruited after a 3-month recruitment period, (2) the estimated study staff's time, and (3) representation of sociodemographic characteristics (e.g., age, sex, race, SES measured by HOUSES index, and rural residence) between subjects recruited via TESRS and those via traditional mailing methods. RESULTS: Median age of randomized subjects (n = 600) was 63 years with 52.0% female and 89.2% non-Hispanic White. Over a 3-month period, results showed consent rate via TESRS was 13% (39/297) similar to 11% (31/295) via standard mailing. However, recruitment was significantly faster with the TESRS approach (median 7 vs 26 days) given the study staff's effort. Study staff's time saved by using TESRS compared to standard mailing approach was estimated at 40 min per subject (equivalent to 200 h for 300 subjects). No significant differences in characteristics of research subjects from the study population were found. CONCLUSION: Our study demonstrated the utility of TESRS as a subject recruitment digital technology which significantly enhanced the recruitment effort while reducing the study staff burden of recruitment while maintaining the consistency of characteristics of recruited subjects. The strategy and support for implementing and testing TESRS in other study settings should be considered.

Geropsychology training at the doctoral level: a program evaluation case example.

While the older adult population continues to grow, psychologists specializing in geropsychology remain a small fraction of the workforce. Facing this reality, it is essential for training programs to better monitor whether their students receive adequate training to serve older adults. The current study describes a brief, logistically feasible, and cost-effective program evaluation conducted within one APA-accredited clinical psychology doctoral program. The evaluation consisted of an online survey of doctoral students (n = 99) that explored their field training experiences with older adults, coursework related to aging, and their overall interest in working with older adults. Students reported significantly less coursework and significantly less field work focused on serving older adults when compared to other age groups. However, students reported a high level of interest in learning about aging, with a total of 73.74% of participants (n = 73) reporting at least some current interest. A number of institutional actions resulted from this evaluation, which demonstrate how a brief evaluation can yield data that is practically useful. This case example provides a useful model for others to follow, and may support other institutions' efforts to evaluate, monitor, and make potential improvements to aging-related training in their own programs.

Chronic inflammation can transform the fate of normal and mutant hematopoietic stem cells.

Chronic inflammation, although subtle, puts the body in a constant state of alertness and is associated with many diseases, including cancer and cardiovascular diseases. It leads hematopoietic cells to produce and release proinflammatory cytokines, which trigger specific signaling pathways in hematopoietic stem cells (HSCs) that cause changes in proliferation, differentiation, and migration. This response is essential when HSCs are needed to produce specific blood cells to eliminate an intruder, such as a pathogenic virus, but mutant HSCs can use these proinflammatory signals to their advantage and accelerate the development of hematologic disease or malignancy. Understanding this complex process is vital for monitoring and controlling disease progression in patients. In the 2023 International Society for Experimental Hematology winter webinar, Dr. Eric Pietras (University of Colorado Anschutz Medical Campus, United States) and Dr. Katherine Y. King (Baylor College of Medicine, United States) gave a presentation on this topic, which is summarized in this review article.

Cardiac autonomic regulation in response to functional power threshold testing in elite cyclists / Regulación autonómica cardiaca en respuesta a la prueba de umbral de potencia funcional en ciclistas deélite

Objective: To evaluate the impact of a functional power threshold test (FTP) on cardiac autonomic regulation indicators in high performance cyclists.Methods: A total of 12 male elite cyclists (mean age 36.1 ± 11.2 years) were recruited. Body composition parameters were measured usingbioimpedancemetry and heart rate variability (HRV) before and after the application of the FTP assessment. Results: We observed that a greater sympathetic nervous system (SNS) index and Stress index on baseline were correlated with a smaller decrease in theparasympathetic nervous system (PNS) activity in response to the FTP test (ρ= 0.69, p = 0.013). Concerning morphological parameters, the skeletalmuscle index (SMI) was the only one that was inversely correlated with ∆PNS (ρ= -0.69, p = 0.02) whereas the muscle-bone index (MBI) displayed apositive correlation with ∆SNS (ρ = 0.82, p = 0.001). In fully adjusted models we found that waist-to-hip ratio (β= 7.90, CI95%[4.16, 11.63], t(8) = 4.88, p =0.001) and SMI significantly influenced ∆PNS (β = -1.38, CI95%[-1.84, -0.92], t(8) = -6.94, p < 0.001), whereas MBI (β= 10.26, CI95%[8.10, 12.42], t(8) =10.96, p < 0.001) and the interaction between the latter and Power achieved during FTP influenced ∆SNS (β = -0.05, CI95%[-0.09, -4.99e-03], t(8) = -2.56, p= 0.033). Conclusion: Our findings indicate that the SMI had a negative effect on the ∆PNS, while the MBI was positively correlated with the ∆SNS in cyclists. Thesefindings suggest that a higher SMI and MBI could have a detrimental impact on the cardiac autonomic response to maximal aerobic exercise in high-performance cyclists, such as FTP.(AU)

Objetivo: Evaluar el impacto de una prueba de umbral de potencia funcional (FTP) sobre los indicadores de regulación autonómica cardiaca en ciclistasde alto rendimiento. Métodos: Se reclutó a un total de 12 ciclistas de élite masculinos (edad media 36.1 ± 11.2 años). Se midieron los parámetros de composición corporalmediante bioimpedanciometría y la variabilidad de la frecuencia cardiaca (HRV) antes y después de la aplicación de la evaluación del FTP. Resultados: Observamos que un mayor índice del sistema nervioso simpático (SNS) e índice de estrés basalmente se correlacionaron con una menordisminución de la actividad del sistema nervioso parasimpático (PNS) en respuesta a la prueba FTP (ρ= 0.69, p = 0.013). En cuanto a los parámetrosmorfológicos, el índice músculo esquelético (SMI) fue el único que se correlacionó inversamente con el ∆PNS (ρ= -0.69, p = 0.02) mientras que el índicemúsculo-hueso (MBI) mostró una correlación positiva con ∆SNS (ρ = 0.82, p = 0.001). En los modelos totalmente ajustados encontramos que la relacióncintura-cadera (β= 7.90, CI95%[4.16, 11.63], t(8) = 4.88, p = 0.001) y el SMI influían significativamente en el ∆PNS (β= -1.38, CI95%[-1.84, -0.92], t(8) = -6.94,p < 0.001), mientras que el MBI (β = 10.26, CI95%[8.10, 12.42], t(8) = 10.96, p < 0.001) y la interacción entre este último y la Potencia alcanzada durante elFTP influían en el ∆SNS (β= -0.05, CI95%[-0.09, -4.99e-03], t(8) = -2.56, p = 0.033). Conclusión: Nuestros hallazgos indican que el SMI tuvo un efecto negativo sobre el ∆PNS, mientras que el MBI se correlacionó positivamente con el ∆SNSen ciclistas. Estos hallazgos sugieren que un mayor SMI y MBI podrían tener un impacto perjudicial en la respuesta autonómica cardíaca al ejercicioaeróbico máximo en ciclistas de alto rendimiento, como el FTP.(AU)

Forecasting hydrologic controls on juvenile anadromous fish out-migration with process-based modeling and machine learning.

River herring (Alosa sp.) are ecologically and economically foundational species in freshwater streams, estuaries, and oceanic ecosystems. The migration between fresh and saltwater is a key life stage of river herring, where the timing and magnitude of out-migration by juveniles can be limited when streams dry and hydrologic connectivity is lost. Operational decisions by water managers (e.g., restricting community water use) can impact out-migration success; however, these decisions are largely made without reliable predictions of outmigration potential across the migration season. This research presents a model to generate short-term forecasts of the probability of herring out-migration loss. We monitored streamflow and herring out-migration for 2 years at three critical runs along Long Island Sound (CT, USA) to develop empirical understandings of the hydrologic controls on out-migration. We used calibrated Soil and Water Assessment Tool hydrologic models of each site to generate 10,000 years of daily synthetic meteorological and streamflow records. These synthetic meteorological and streamflow data were used to train random forest models to provide rapid within-season forecasts of out-migration loss from two simple predictors: current spawning reservoir depth and the previous 30-day precipitation total. The resulting models were approximately 60%-80% accurate with a 1.5-month lead time and 70-90% accurate within 2 weeks. We anticipate that this tool will support regional decisions on spawning reservoir operations and community water withdrawals. The architecture of this tool provides a framework to facilitate broader predictions of the ecological consequences of streamflow connectivity loss in human-impacted watersheds.

Diagnosis and surgical management of pericardial constriction after cardiac surgery.

OBJECTIVES: Previous cardiac surgery is an increasingly common etiology of constrictive pericarditis, but there is a paucity of data on clinical presentation and outcome of surgical treatment. METHODS: We reviewed data of 263 patients who underwent pericardiectomy for postoperative constriction from January 1, 1993, through July 1, 2017. Outcomes of interest were early and late mortality, as well as features of clinical presentation. RESULTS: Median patient age was 64 (56-72) years, and the median interval between previous operation and pericardiectomy was 2.7 years (range, 0-54 years). Previous operations included coronary artery bypass grafting in 114 (43%), valve surgery in 85 (32%), combined coronary artery bypass grafting and valve surgery in 33 (13%), and other procedures in 31 (12%). Common presentations were symptoms of right heart failure in 221 (84%) or dyspnea in 42 (16%). Moderate-to-severe tricuspid valve regurgitation was present in 108 (41%) patients. There were 14 (5.5%) deaths within 30 days postoperatively, and survival at 5 and 10 years postoperatively was 61% and 44%. On multivariate analysis, older age (P = .013), diabetes (P = .019), and nonelective pericardiectomy within 2 years of cardiac surgery (P < .001) were associated with decreased long-term survival. CONCLUSIONS: Pericardial constriction after cardiac surgery can present at any interval postoperatively. Symptoms and signs of right heart failure in patients with previous cardiac surgery should alert physicians to the possibility of pericardial constriction followed by a correct diagnosis. Pericardiectomy performed urgently following cardiac operation has poor long-term outcomes.